Anorexia Nervosa (AN) is a serious disorder with substantial morbidity and mortality. While there is agreement in the field that weight restoration is a treatment priority, no particular therapeutic approach for patients with AN has clear empirical support. The NIMH has identified AN as an illness in need of treatment research initiatives. This application for an R21 exploratory/development grant for mental health intervention research describes a proposal to develop and pilot an innovative treatment for underweight outpatients with AN using atypical antipsychotic medication. This project proposes a collaborative study at two sites, Columbia University and The University of Toronto, both well known for the study and treatment of eating disorders. The project will formally evaluate the tolerability and acceptability, and make a general estimate regarding efficacy, of the atypical antipsychotic agents olanzapine and aripiprazole. Additionally, it will assess contributors to medication compliance and develop interventions to decrease patients' reluctance to take a medication associated with weight gain. The initial year of the project will be used to compare olanzapine, a medication reported to have promise in AN, with aripiprazole, another atypical antipsychotic medication without significant weight gain as a side effect. During this phase of the project, an open randomized comparison trial will be conducted in order to develop information regarding benefits, tolerability, acceptability, safety, and appropriate dosage. These data will be used to select either olanzapine or aripiprazole for further evaluation. Additionally, the early phase of the project will include development of treatment strategies to improve acceptability and compliance for new, potentially useful medications. In the second and third years of the project, a placebo-controlled pilot study of the selected medication will be conducted to obtain controlled data about general efficacy and to estimate effect size in preparation for a larger and more definitive clinical trial.